1. Field of Invention
The present invention relates to an automated method for carrying out reactions with high spatial resolution on libraries of different materials and for analysis of the products obtained using a simple robot system and an analyzer, for example a mass spectrometer.
In particular, the method relates to determining the activity and selectivity of solid or molecular materials to be used as catalysts for gas phase reactions. In an exemplary embodiment of the invention, a commercial pipetting or synthesis robot is used to position the sensor lines in order to examine reactions on a combinatorial library with high spatial resolution. The method according to the invention is characterized, in particular, by the simplicity of its set-up that is not restricted to a specific type of reactor as well as by the ease with which it is possible to switch between synthesis and screening.
2. Description of Related Art
While combinatorial chemistry has established itself as an important tool for the development of new compounds in the areas of organic, biochemical and pharmaceutical chemistry (see, e.g., the special issue: Combinatorial Chemistry, Acc. Chem. Res., 1996, 29; G. Lowe, Chemical Society Reviews, 1995, 24(5), 309; S. R. Wilson, A. W. Czamik, Combinatorial Chemistry—Synthesis and Application, John Wiley & Sons, 1997), only a few examples of using combinatorial methods are known in the areas of inorganic solid state synthesis, materials research and catalyst development. The prior-art is defined by the manufacturing of libraries of materials by means of physical vapor deposition methods and by combining these methods with masking techniques, or, in the field of wet chemistry, by using ink-jet techniques, or by employing synthesis robot systems. Here, the size of libraries varies from below 100 components to 25,000 components per library. The analysis or characterization of specific properties is essential for the analysis of such libraries. Due to the dimensional miniaturization that is mandatory for the implementation of large libraries of materials, only minimal amounts of sample are available.
As of yet, only few examples are prominent with respect to the effort to record the catalytic properties of materials within combinatorial libraries of materials. The emitted heat of reaction on components of a library of catalysts can be imaged by means of IR-thermography, corrected for emissions, with spatial resolution and great sensitivity, both for gas-phase reactions with heterogeneous catalysts (A. Holzwarth, H. W. Schmidt, W. F. Maier, Angew. Chem. 1998, 110, 2788) and in fluid phases with enzyme catalysts (M. T. Reetz, M. H. Becker, K. M. Kuehling, A. Holzwarth, Angew. Chem. 1998, 110, 2792). However, using IR-thermography only allows for conclusions on the relative reactivity of the components of a library. This is insufficient whenever secondary or parallel reactions have to be taken into account, such as in the case of complete oxidation used for the search for selective oxidation catalysts. Therefore, it is desirable to have methods of analysis at hand, besides IR-thermography, that allow for the recording of chemical selectivities with high spatial resolution directly on the library, preferably in an automated manner.
The recent work of Weinberg et al. describes the application of methods of mass spectrometry for high speed scanning of libraries of catalysts (P. Cong, R. D. Coolen, Q. Fan, D. M. Giaquinta, S. Guan, E. W. McFarland, D. M. Poojary, K. Self, H. W. Turner, W. H. Weinberg, Angew. Chem. 1999, 111, 508; W. H. Weinberg, E. W. McFarland, P. Cong, S. Guan (Symyx Technologies), WO-A 98/15969 A2, 1998). Using mass spectrometry, Weinberg and collaborators have detected the CO2 formed during the oxidation of CO with O2 or NO at metallic alloys of Rh, Pd, Pt and Cu, as well as the educt gases. The system described in more detail in the aforementioned patent application relates to the spatially separated feed of educts and the removal of products via holes in the mass spectrometer and is expensive and requires significant implementation efforts. This system is specifically designed for yielding results even for the smallest amount of catalyst, down to 2–4 μg per catalyst element. This requires a costly modification of the mass spectrometer by introducing a second quadrupol filter (“ion guide”) as well as the construction of a system of separated vacuum chambers for separating synthesis, sample preparation and the actual screening. Thus, a direct transfer of the library is possible from the preparation area to the mass spectrometer. However, remote handling of the sample and establishing realistic reaction conditions is exacerbated under this design. In the aforementioned publication (oxidation of CO with O2 or NO to yield CO2), only catalytic activities are discerned but no conclusions are possible on differences in selectivities of individual components of the library. In complex reactions with several possible products (often produced in low yield) where the products are very different or where the products have similar selectivities, this method has failed because the quantity of product is too small.